Stroke is the most significant complication of sickle cell disease (SCD) in children with the potential for major morbidity and mortality. The recent two decades have witnessed tremendous advancements in understanding the pathophysiology of stroke, risk stratification of children and the role of timely preventative interventions. The aetiopathogenesis, types of stroke and specific risk factors are reviewed here with special emphasis on the role of transcranial Doppler ultrasonogram in the early identification of at-risk children. Published studies on primary and secondary prevention of stroke in children with SCD are analysed with respect to the levels of evidence, in favour of preventative and therapeutic strategies. The roles of the neurologist and the neurosurgeon are highlighted.